Our laboratory is engaged in studies on taurine and carnitine in the heart. We are and will continue to pursue studies on pathophysiological factors and phamacological agents which regulate carnitine and taurine concentrations in the heart. Two biological models are being used for uptake studies: 1. Adult beating isolated rat heart cells and; 2. Fetal mouse hearts. A number of competitive and non-competitive inhibitors of taurine and carnitine uptake have been studied. It has been shown that carrier mediated uptake systems for taurine and carnitine are present in our biological models. These systems are saturable, energy and temperature dependent. The taurine system is sodium dependent whereas the carnitine system is not. Taurine has been found to exclude sodium entry into and prevent potassium exit from heart cells. Carnitine is a necessary factor in the oxidation of long chain fatty acids in the heart. A stimulator of carnitine uptake by the heart has been identified and is being characterized. The effects of a number of hormones (insulin, thyroxine, glucagon, cortisol growth hormone) are being studied on uptake of taurine in a number of animal models (hypertensive rats, thyrotoxic rats and rats treated with diptheria toxin and doxorubicin). Carnitine will be similarly studied. In addition to uptake of both carnitine and/or taurine the effects of various drugs, toxins, hormones on substrate use by the heart will be studied. We have planned mechanical studies using a fetal mouse heart with implanted microcrystals in a number of the above studies. This will enable a correlation of metabolic and mechanical effects relative to taurine and carnitine alterations.